The supraspinal subcortical structures and pathways essential for cranial, somatic and visceral pain sensation and associated aversive behavior in mammals are not known. Physiological, anatomical and clinical studies suggest two major systems originating from ascending fibers in the ventrolateral spinal cord: (1) A direct spinothalamic system projecting to the posterior (PO) and medial-intralaminar thalamus and (2) a spino-reticulo-thalamic system projecting via nucleus gigantocellularis (NGC) to the centre median-parafascicular thalamic complex. The physiologic interaction of these two systems will be studied in anesthetized cat and squirrel monkey, testing the effect of lesions and stimulation of each system. This will be followed by a combined behavioral and electrophysiological analysis of the effects of chronic NGC and/or PO lesions. The results will guide more detailed unit analysis of cranial, somatic and visceral inputs to relevant structures and the peripheral and CNS influences modulating their activity. A system for simultaneously recording and correlating single unit activity and operant pain behavior will be developed for the awake squirrel monkey. These studies will focus on the behavioral and neurophysiological effects of peripheral and CNS inputs which influence neural activity in structures essential for painrelated behavior.